Abstract

Preterm birth (delivery at less than 37 weeks of gestation) is the leading cause of
infant mortality worldwide. So far, the application of animal models to understand
human birth timing has not substantially revealed mechanisms that could be used to
prevent prematurity. However, with amassing data implicating an important role for
genetics in the timing of the onset of human labor, the use of modern genomic approaches,
such as genome-wide association studies, rare variant analyses using whole-exome or
genome sequencing, and family-based designs, holds enormous potential. Although some
progress has been made in the search for causative genes and variants associated with
preterm birth, the major genetic determinants remain to be identified. Here, we review
insights from and limitations of animal models for understanding the physiology of
parturition, recent human genetic and genomic studies to identify genes involved in
preterm birth, and emerging areas that are likely to be informative in future investigations.
Further advances in understanding fundamental mechanisms, and the development of preventative
measures, will depend upon the acquisition of greater numbers of carefully phenotyped
pregnancies, large-scale informatics approaches combining genomic information with
information on environmental exposures, and new conceptual models for studying the
interaction between the maternal and fetal genomes to personalize therapies for mothers
and infants. Information emerging from these advances will help us to identify new
biomarkers for earlier detection of preterm labor, develop more effective therapeutic
agents, and/or promote prophylactic measures even before conception.